1H-NMR relaxation times and water compartmentalization in experimental tumor models

The present studies were conducted with RIF-1, M5076 and Panc02 subcutaneous tumor models to assess the relationship between tissue-free water compartmentalization and observed tissue T1 and T2 changes at 10 MHz. Observed T1 was shown to correlate directly with total extracellular water and interstitial water volumes. T1 and T2 were also inversely related to intracellular water volumes. T1 and T2 decreases after dexamethasone treatment were, however, most closely correlated with changes in tumor extracellular water and not changes in cell or total water volumes. Studies to assess Gd-DTPA-dimeg dose dependent T1 and T2 modification in model serum protein solutions indicated that although the Gd concentration that reduced T2 by 50% was about 2.5 fold greater than that required to reduce T1 equally, the of the concentration dependent T1 and T2 modifications were similar. In studies with tumor models, the injected dose of Gd-DTPA-dimeg that reduced T1 by 50% was inversely correlated with tumor extracellular water volumes. The slopes for dose dependent T1 modification in all tumors were similar and similar to that observed for model protein solutions. Gd-DTPA-dimeg had a different effect on observed T2 values for the 3 tumor models. Exponential slopes were about twice that observed for T2 modification of serum protein solutions, and Gd-DTPA-dimeg doses that reduced observed tumor T2 ranged from 9 to 50 times that necessary to similarly reduce T1. The results from these studies indicate that the observed T1, for these tumors, was dominated by relaxation of water protons in interstitial water but that the observed T2 was most strongly influenced by proton relaxation in water compartments that were unavailable to the Gd labeled probe.     

Regional variation in rat brain proton relaxation times and water content

Relaxation times (T1 and T2) and water content are measured in frontal cortex, amygdaloid cortex, hippocampus, mid-brain and cerebellum of rat brain. Differences are found in relaxation times, between areas containing a mixture of grey and white matter, and grey matter only. Differences were also found between certain grey matter areas. Relaxation times correlated with water content.     

Evaluation of water content by spatially resolved transverse relaxation times of human articular cartilage

Non-invasive assessment of cartilage properties, specifically water content, could prove helpful in the diagnosis of early degenerative joint diseases. Transverse relaxation times T(2) of human articular cartilage (34 cartilage slices of three donors) were measured on a pixel-by-pixel basis in a clinical whole body MR system in vitro. In vivo feasibility to measure quantitative T(2) maps was shown for human patellar cartilage. The relaxation times of cartilage with collagen in the radial zone oriented perpendicular to the magnetic field increased from approximately 10 ms near the bone to approximately 60 ms near the articular surface. Cartilage water content of the tibial plateau and femoral condyles could be determined from the correlation with T(2) (R(2) = 0.71) with an error of approximately 2 wt.%. In vivo, directional variation would need to be considered. If confirmed in vivo, T(2) measurements could potentially serve as a non-invasive tool for the evaluation of the status and distribution of water content in articular cartilage.     

Effect of tissue fat and water content on nuclear magnetic resonance relaxation times of cardiac and skeletal muscle

Understanding tissue determinants that affect the nuclear magnetic resonance (NMR) properties of myocardium would improve noninvasive characterization of myocardial tissue. To determine if NMR relaxation times would reflect changes in tissue fat content, two experimental models were investigated. First, an idealized model using mixtures of beef skeletal muscle and beef fat was studied to investigate the effects of a wide range of tissue fat content. Second, myocardium with varying fat content from hogs raised to have varying degrees of ponderosity was analyzed. Tissue fat and water contents and spin-lattice (T1) and spin-spin (T2) relaxation times at 20 MHz were measured. The skeletal muscle/fat mixtures ranged in fat content from 35% to 95% with water content variations from 50% to 75%. Water content decreased as fat content increased. A significant inverse linear relationship was found between T1 and sample fat content (r = -0.997). Spin-spin relaxation times showed a significant positive curvilinear relationship with fat content (r2 = 0.96). In the animal experiments, 18 hogs were studied with samples obtained from both right and left ventricular (LV) free walls, with care taken to avoid epicardial fat. Myocardial fat content ranged from 3% to 25%. A significant correlation was found between LV fat content and corrected LV mass (r = 0.62), which suggested that the increase in LV mass could be explained, at least in part, by changes in myocardial fat content. Similar to the muscle/fat mixture model, a significant positive curvilinear relationship was found between myocardial T2 and tissue fat content (r2 = 0.67) for all the myocardial samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

The measurement of extracellular water volumes in tissues by gadolinium modification of 1H-NMR spin lattice (T1) relaxation

The present studies were conducted in RIF-1, M5076 and Panc02 murine tumor models to compare extracellular water measurements made by 51Cr-EDTA dilution techniques and a new method which exploits the concentration dependent modification of 1H-NMR proton relaxation by Gadolinium-DTPA-dimethyl glucamine (Gd-DTPA-dimeg) in plasma and tissues. The time dependent changes in T1 modification in tissue and plasma were determined at various intervals after i.v. injection of 0.1 ml of 100 mM Gd-DTPA-dimeg and Gd concentrations determined from standard curves of Gd concentration dependent T1 modification of mouse plasma. Comparison of tissue and plasma Gd concentrations permitted the calculation of Gd-DTPA-dimeg distribution volumes. In unperturbed RIF-1, M5076 and Panc02 tumors, Gd-DTPA-dimeg distribution volumes determined by the T1 modification technique were similar to extracellular water spaces determined by 51Cr-EDTA dilution assays. In mouse liver, the 51Cr-EDTA assay resulted in artifactually high extracellular water space estimates due to internalization of the probe; Gd-DTPA-dimeg distribution volumes determined in liver with both the 153Gd-DTPA-dimeg and by the T1 modification method were approximately 150 ul/gram. The Gd-DTPA-dimeg T1 modification method also provided good approximations of changes in extracellular water volumes in RIF-1 tumors after dexamethasone and cyclophosphamide treatments. These results indicate that Gd-DTPA-dimeg modification of proton relaxation may be extremely useful for monitoring changes in tumor water dynamics during cancer therapy.     

Determination of relaxation times of N2 (v=1) level in presence of water vapor

The vibrational kinetics in CO₂-N₂-H₂O and CO-N₂-H₂O mixtures behind a reflected shock were investigated in the temperature range 500–1500°K by measurement of the intensity of the infrared emission of the gas. The vibrational relaxation time of nitrogen after collision with water molecules is obtained. The reasons for the disagreement of the presently available experimental data on the rate of this process are analyzed.Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Fizika, No. 6, pp. 84–89, June, 1978.     

The effects of changing water content,relaxation times,and tissue contrast on tissue segmentation and measures of cortical anatomy in MR images

Water content is the dominant chemical compound in the brain and it is the primary determinant of tissue contrast in magnetic resonance (MR) images. Water content varies greatly between individuals, and it changes dramatically over time from birth through senescence of the human life span. We hypothesize that the effects that individual- and age-related variations in water content have on contrast of the brain in MR images also have important, systematic effects on in vivo, MRI-based measures of regional brain volumes. We also hypothesize that changes in water content and tissue contrast across time may account for age-related changes in regional volumes, and that differences in water content or tissue contrast across differing neuropsychiatric diagnoses may account for differences in regional volumes across diagnostic groups.     

Assessment of interstitial water content of articular cartilage with T1 relaxation

The interstitial water content typically increases in the early degeneration of articular cartilage. Previously, T₂ relaxation has been related to water content, yet it is known to be strongly affected by the collagen orientation. Articular cartilage plugs from the bovine patella, femur and tibia (N=20) were mapped for T₁ and T₂ at 9.4 T to test the ability of T₁ relaxation to reflect cartilage water content. As a reference, water and proteoglycan (PG) contents were determined. Significant (P<.01) linear associations were demonstrated between the relaxation rates and tissue water content (R₁: r=−.81, R₂: r=−.60) and PG content (R₁: r=.75). After adjustment for the tissue water content, partial correlation analysis did not show significant associations between the relaxation rates and tissue PG content. After the effect of PGs was removed, significant (P<.05) linear correlation between the relaxation rates and tissue water content (R₁: r=−.48, R₂: r=−.50) was observed. Thus, the spin-lattice relaxation rate is proposed to provide a biomarker for water content in articular cartilage.     

Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements

The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty in applying this technique in vivo is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of backscattering properties from blood microstructures. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure factor. With in vitro experiments, the method gave satisfactory estimates with relative errors below 22% for attenuations between 0.101 and 0.317 dBcmMHz, signal-to-noise ratios>28 dB and kR<2.7 (k being the wave number and R the aggregate radius).     

Flow dynamics of red blood cells and their biomimetic counterparts

We review recent experimental, theoretical, and computational studies of red blood cells and their mimics, vesicles and capsules, in flow. We focus on the continuum approach in modeling cell deformability and blood rheology.     

Analysis of membrane tank-tread of nonspherical capsules and red blood cells

We present an analysis of membrane motion of deformable capsules and red blood cells suspended in a linear shear flow and undergoing swinging and tumbling motions using three-dimensional numerical simulations. This study is motivated by the theory of the shape-preserving cells which predicts that the direction of the membrane rotation depends on the cell orientation and reverses at every 45° inclination angle of the cell major axis with respect to the external flow direction. By considering large deformation of capsules and red blood cells, here we investigate how the shape oscillation affects the time dependence and the direction reversal of the membrane rotation. We find that the membrane tank-tread is highly time-dependent in nature and synchronized with the time-dependent deformation. The maximum and minimum of the tank-tread velocity occur at and near the minimum and maximum deformation, respectively. For the swinging capsules and red blood cells, the direction of the membrane rotation is always along the direction of the external fluid rotation; however, a direction reversal occurs during the tumbling motion in which case the membrane rotates in the direction of the external fluid rotation when the major axis is mostly in the extensional quadrant of the shear flow, and in the opposite direction when it is mostly in the compressional quadrant. Unlike the theory which predicts the direction reversal at every 45° inclination angle irrespective of the control parameters, namely, the capillary number, viscosity ratio, and asphericity, we find that the angle at which the direction reversal occurs depends on these parameters. In particular, if the tumbling motion occurs by decreasing the capillary number, the membrane rotation is in the direction of the external flow rotation in the entire extensional quadrant, but in the opposite direction in the compressional quadrant, irrespective of the specific values of the capillary number. If the tumbling motion occurs by increasing the viscosity ratio and asphericity, the angle at which the direction reversal occurs depends on the specific values of these two parameters. The spatial variation of the tank-tread velocity also is analyzed and attributed to the straining motion of the external flow.      

Changes of relaxation times T1 and T2 in rat tissues after biopsy and fixation

NMR spectroscopical measurements of relaxation times were conducted on muscle, intestine, fatty tissue and cerebral cortex and white matter of the rat at various time intervals following removal of the tissue. It appeared that most tissues can be stored at 4 degrees C up to 24 hours without noticeable effects on NMR relaxation parameters. Exceptions are the T2 of muscle and the T1 and T2 of intestine, which tended to change in the first hour after biopsy. Relaxation parameters change considerably after fixation of the tissues. Therefore the effects of fixation have to be taken into account when carrying out NMR measurements on fixed tissues.